Chuanyong Liu

Estradiol upregulates the expression of oxytocin receptor in colon in rats

The study was designed to investigate the effect of estradiol on the excitatory effect of oxytocin (OT) on colon motility. Female Wistar rats were used, and some of them were ovariectomized (OVX) and treated with vehicle or estradiol (E(2)). A plastic balloon made of condom was inserted into colon to monitor the change of colonic pressure in vivo. Longitudinal muscle strips of distal colon were prepared to monitor the spontaneous contraction of colon in vitro. Expression of OT receptor (OTR) was investigated by Western blot analysis. Expression of OTR mRNA was detected by RT-PCR. Immunohistochemistry was used to locate OTR. In OVX rats, pretreatment of E(2) (4-100 microg/kg sc) dose-dependently increased the excitatory effect of OT on colon motility both in vivo and in vitro and increased the expression of OTR and OTR mRNA in colon. Systemic administration of OT excited the colon motility in vivo in rats at perioda of proestrus and estrus but did not influence it at diestrus period, when the concentration of plasma E(2) was lowest in the estrous cycle. Pretreatment of atosiban, the specific OTR antagonist, and TTX, the blocker of voltage-dependent sodium channel on nerve fiber, attenuated the excitatory effect of OT on colon motility. OTR was located in myenteric plexus of colon. These results suggested that E(2) increased the excitatory effect of OT on colon motility by upregulating the expression of OTR in myenteric plexus.

H2S modulates duodenal motility in male rats via activating TRPV1 and KATP channels

H2S induces vasodilatation by opening KATP channels but it may also affect other ion channels. The aim of this study was to investigate the effect of H2S on intestinal motility in rats and its underlying mechanism.

Sensitization of mesenteric afferents to chemical and mechanical stimuli following systemic bacterial lipopolysaccharide

Abstract  Background:  The mechanisms underlying endotoxin‐induced hyperalgesia remain unknown. We aimed to study the mechanisms underlying the sensitizing action of lipopolysaccharide (LPS) on intestinal afferent responses to mechanical and chemical stimuli.

Ethanol Upregulates iNOS Expression in Colon Through Activation of Nuclear Factor‐kappa B in Rats

BACKGROUND Alcohol inhibits colonic motility but the mechanism is unknown. The goal of this study was to test the possibility that nuclear factor-kappa B (NF-kappaB) is involved in the upregulation of inducible nitric oxide synthase (iNOS) expression induced by ethanol in colon. METHODS The isometric contraction of longitudinal muscle strips of proximal colon (LP) was monitored by polygraph. Western blot analysis was used to measure the amount of iNOS and I-kappaB in the cytoplasm and P65 in the nucleus. Immunohistochemistry was applied to locate iNOS in colon. RESULTS Ethanol (87mM) inhibited the contraction of LP. Pretreatment of S-methylisothioure (SMT) (1 mM), a specific iNOS inhibitor, Pyrrolidine dithiocarbamate (PDTC) (10 mM) and BAY11-7082(10 mM), specific inhibitors of NF-kappaB significantly reversed the inhibitory effect of ethanol on LP contraction. Ethanol increased the amount of iNOS and content of NO in colon, and these effects were attenuated by pretreatment of PDTC. Following ethanol administration, the amount of I-kappaB in the cytoplasm decreased, but that of P65, the subunit of NF-kappaB in the nucleus, increased. The iNOS was located in the cell body of myenteric plexus in colon. CONCLUSION Ethanol inhibited the contraction of LP in colon mainly through activation of NF-kappaB, the subsequent upregulation of iNOS expression and increase of NO release in myenteric plexus.

Differential afferent sensitivity to mucosal lipopolysaccharide from Salmonella typhimurium and Escherichia coli in the rat jejunum

Abstract  Postinfectious irritable bowel syndrome may develop subsequent to acute bacterial enteritis. We therefore hypothesized that intestinal afferents may develop hypersensitivity upon exposure to luminal lipopolysaccharide (LPS) from pathogens but not from commensal bacteria and that this may be prostaglandin mediated. Extracellular recordings of jejunal afferents were obtained in vivo from male Wistar rats (n = 5 per group; 300–400 g). Lipopolysaccharide from Escherichia coli (E‐LPS), Salmonella typhimurium (S‐LPS) or vehicle were infused into the intestinal lumen at 5 mg mL−1. The selective 5‐HT3‐receptor agonist 2‐methyl‐5‐HT (2m5‐HT, 15 μgkg−1, i.v.) was administered at 15‐min intervals before and up to 2 h after S‐LPS administration. Intraluminal E‐LPS had no effect on mesenteric afferent nerve discharge at baseline. By contrast, afferent discharge increased from 21.7 ± 0.3 impsec−1 to 28.8 ± 3.4 impsec−1 40 min after S‐LPS administration (mean ± SEM; P < 0.05) and reached 38.8 ± 4.1 impsec−1 after 2 h (P < 0.05). The afferent response to 2m5‐HT was enhanced 30 min following S‐LPS by 30.9 ± 3.9% (P < 0.05) and remained elevated thereafter. The increase in baseline discharge and sensitivity to 2m5‐HT following S‐LPS was prevented by pretreatment with naproxen (COX inhibitor, 10 mgkg−1 i.v.) or AH‐6809 (EP1/EP2 receptor antagonist, 1 mg kg−1). Intestinal afferents do not alter their discharge rate to LPS from E. coli but to LPS from the pathogenic bacterium S. typhimurium. The latter response entails afferent sensitisation to 2m5‐HT that depends on prostanoid release. This acute sensitisation may prime the intestinal afferent innervation for a later development of persistent hypersensitivity.

V1 receptor in ENS mediates the excitatory effect of vasopressin on circular muscle strips of gastric body in vitro in rats

The purpose of this study was to localize vasopressin (VP) V(1a) receptor in stomach and to characterize the role of VP in the regulation of gastric motility in rats. Double staining was used to locate the V(1a) receptor in the gastric body of the rat. The contraction of the circular muscle strips of gastric body was monitored by a polygraph. V(1a) receptor was expressed on the neurons of myenteric plexus of the gastric body. VP (10(-10)-10(-6) M) caused a concentration-dependent contractile effect on the circular muscle strips of gastric body in vitro. V-1880 ([deamino-Pen(1), O-Me-Tyr(2), Arg(8)]-Vasopressin, 10(-7) M), a V(1) receptor antagonist, inhibited the spontaneous contraction of the strips. Tetradotoxin (TTX, 10(-6) M) and V-1880 (10(-7) M) abolished the excitatory effect of VP. Atropine (10(-6) M) partially inhibited VP-induced excitatory effect on the muscle strips but hexamethonium (10(-4) M) did not influence it. These results suggest that V(1a) receptor was expressed on the neurons of myenteric nerves. The cholinergic nerve was involved in the excitatory effect of VP on the contraction of gastric body.

Efficient and accurate treatment of electron correlations with correlation matrix renormalization theory

We present an efficient method for calculating the electronic structure and total energy of strongly correlated electron systems. The method extends the traditional Gutzwiller approximation for one-particle operators to the evaluation of the expectation values of two particle operators in the many-electron Hamiltonian. The method is free of adjustable Coulomb parameters, and has no double counting issues in the calculation of total energy, and has the correct atomic limit. We demonstrate that the method describes well the bonding and dissociation behaviors of the hydrogen and nitrogen clusters, as well as the ammonia composed of hydrogen and nitrogen atoms. We also show that the method can satisfactorily tackle great challenging problems faced by the density functional theory recently discussed in the literature. The computational workload of our method is similar to the Hartree-Fock approach while the results are comparable to high-level quantum chemistry calculations.

Nitric oxide donor protects against acetic acid-induced gastric ulcer in rats via S-nitrosylation of TRPV1 on vagus nerve

This study was conducted to investigate the effects of nitric oxide (NO) in acetic acid-induced gastric ulcer of rats and the underlying mechanisms. We found that peritoneal injection of sodium nitroprusside (SNP), a NO donor, decreased the ulcer area, inflammatory cell infiltration and MPO degree in acetic acid-induced gastric ulcer in rats. This effect was abolished by a transient receptor potential vanilloid 1 (TRPV1) antagonist or prior subdiaphragmatic vagotomy. SNP increased the jejunal mesenteric afferent discharge in a dose-depended manner, which was largely diminished by pretreatment of S-nitrosylation blocker N-ethylmaleimide, TRPV1 antagonist capsazepine, genetic deletion of TRPV1, or vagotomy. Whole-cell patch clamp recording showed that SNP depolarized the resting membrane potential of NG neurons, and enhanced capsaicin-induced inward current, which were both blocked by N-ethylmaleimide. Our results suggest that NO donor SNP alleviates acetic acid-induced gastric ulcer in rats via vagus nerve, while S-nitrosylation of TRPV1 may participate in this route. Our findings reveal a new mechanism for vagal afferent activation, and a new potential anti-inflammatory target.

The antinociception of oxytocin on colonic hypersensitivity in rats was mediated by inhibition of mast cell degranulation via Ca(2+)-NOS pathway.

This study was conducted to investigate the effects of oxytocin (OT) on visceral hypersensitivity/pain and mast cell degranulation and the underlying mechanisms. We found that oxytocin receptor (OTR) was expressed in colonic mast cells in humans and rats, as well as in human mast cell line-1 (HMC-1), rat basophilic leukemia cell line (RBL-2H3) and mouse mastocytoma cell line (P815). OT decreased 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced visceral hypersensitivity, colonic mast cell degranulation and histamine release after mast cell degranulation in rats. Also, OT attenuated the compound 48/80 (C48/80)-evoked histamine release in P815 cells and inward currents, responsible for the mast cell degranulation, in HMC-1, RBL-2H3 and P815 cells. Moreover, these protective effects of OT against visceral hypersensitivity and mast cell degranulation were eliminated by coadministration of OTR antagonist atosiban or a nonselective inhibitor of nitric oxide synthase (NOS), NG-Methyl-L-arginine acetate salt (L-NMMA). Notably, OT evoked a concentration-dependent increase of intracellular Ca2+ in HMC-1, RBL-2H3 and P815 cells, which was responsible for the activation of neuronal NOS (NOS1) and endothelial NOS (NOS3). Our findings strongly suggest that OT might exert the antinociception on colonic hypersensitivity through inhibition of mast cell degranulation via Ca2+-NOS pathway.

Long-term downregulation of protease-activated receptor-2 expression in distal colon in rats following bacillary dysentery

The aim of this study was to determine changes of PAR-2 expression in distal colon and the sensitivity of colonic muscle to SLIGRL-NH2, the PAR-2-activating peptide (PAR-2-AP) following bacillary dysentery. Shigella flexneri was administrated intragastrically in healthy male rats to induce bacillary dysentery. The effect of SLIGRL-NH2 on the motility of colonic muscle strips were examined. The expression of PAR-2 was determined by immunohistochemistry and Western blotting. Intragastric administration of S.flexneri induced acute inflammation at the mucosa of the distal colon at 4-11 days, and the inflammation disappeared 18 days later. PAR-2-AP-induced TTX insensitive relaxation of the colonic muscle strips. This inhibitory effect on colonic circular muscle strips was reduced on days 11-35, but the carbachol-induced contraction did not change. PAR-2 was located at the colon smooth muscles cells and myenteric nerve plexus. The amount of PAR-2 expression in distal colon was down regulated on days 11-35. These data indicated that bacillary dysentery exerted a long-term downregulation on the expression of PAR-2 in distal colon. This might be the reason of the low sensitivity of the colon circular muscle strips to the PAR-2-AP-induced relaxation following intragastric administration of S.flexneri.